title: The fine-tuning of thermosensitive and degradable polymer micelles for enhancing intracellular uptake and drug release in tumors.
abstract: Focusing on high temperature and low pH of tumor tissue, we prepared temperature and pH responsive poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide-b-lacitde) (PID(118)-b-PLA(59)) and poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide-b-ε-caprolactone) (PID(118)-b-PCL(60)) diblock copolymers with symmetric hydrophobic blocks by the reversible addition-fragmentation chain transfer (RAFT). The corresponding dual functional polymeric micelles were fabricated by dialysis methods. Their well-defined core-shell structure was characterized by (1)H NMR in D(2)O and further confirmed by TEM. Their structural and physical chemistry properties such as diameters (D), core corona dimension (R(core), R(shell)), distribution (PDI), M(w), aggregation number (N(agg)), second virial coefficient (A(2)), critical micellization concentration (CMC) and z-potential were firstly systemically investigated by dynamic and static laser light scattering. The volume phase transition temperature (VPTT) was around 40 °C above which the intracellular uptake of adriamycin (ADR) was significantly enhanced. Both flow cytometry and fluorescent microscopy showed that the ADR transported by these micelles was about 4 times higher than that by the commercial ADR formulation Taxotere®. In vitro cytotoxicity assay against N-87 cancer cell and confocal laser scanning microscopy (CLSM) also confirmed such promoting efficiency. In addition, it was interesting to find that cell surviving bounced back as T = 42 °C due to the inter-micellar aggregation. The well clarified mechanism strongly support that our finely tailored dual functional core-shell micelles are potent in enhancing cellular uptake and drug release.
authors.affiliation: International Joint Cancer Institute, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, PR China. liwei.dds@gmail.com
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Li
authors.forename: Jie
authors.initials: J
authors.lastname: Gao
authors.forename: Bohua
authors.initials: B
authors.lastname: Li
authors.forename: Yu
authors.initials: Y
authors.lastname: Xia
authors.forename: Yanchun
authors.initials: Y
authors.lastname: Meng
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Yu
authors.forename: Huaiwen
authors.initials: H
authors.lastname: Chen
authors.forename: Jianxin
authors.initials: J
authors.lastname: Dai
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: Yajun
authors.initials: Y
authors.lastname: Guo
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004317:Doxorubicin / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008823:Micelles; D009369:Neoplasms / Q000188:drug therapy*; D011108:Polymers / Q000737:chemistry*; D013696:Temperature
chemical_list: D000903:Antibiotics, Antineoplastic; D003692:Delayed-Action Preparations; D008823:Micelles; D011108:Polymers; D004317:Doxorubicin